Abstract
Angiotensin II (Ang II) causes cardiomyocytes hypertrophy. Cardiac beta-myosin heavy chain (beta-MyHC) gene expression can be altered by Ang II. The molecular mechanisms are not completely known. Reactive oxygen species (ROS) are involved in signal transduction pathways of Ang II. However, the role of ROS on Ang II-induced beta-MyHC gene expression remains unclear. Here we found that Ang II increased beta-MyHC promoter activity and it was blocked by Ang II type 1 receptor antagonist losartan. Ang II dose-dependently increased the intracellular ROS. Cardiomyocytes cotransfected with a dominant negative mutant of Ras (RasN17), Raf-1 (Raf301), or a catalytically inactive mutant of extracellular signal regulated kinase (mERK2) inhibited Ang II-induced beta-MyHC promoter activity, indicating Ras/Raf/ERK pathway was involved. Antioxidants such as catalase or N-acetyl-cysteine decreased Ang II-activated ERK phosphorylation and inhibited Ang II-induced beta-MyHC promoter activity. These data indicate that Ang II increases beta-MyHC gene expression in part via the generation of ROS.
Copyright 2001 Academic Press.
MeSH terms
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Angiotensin II / pharmacology*
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Angiotensin Receptor Antagonists
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Animals
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Animals, Newborn
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Antihypertensive Agents / pharmacology
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Antioxidants / pharmacology
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Cells, Cultured
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Dose-Response Relationship, Drug
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Fluoresceins
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Fluorescent Dyes
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Gene Expression / drug effects
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Mitogen-Activated Protein Kinase 1 / genetics
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Mitogen-Activated Protein Kinase 1 / metabolism
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinases / metabolism
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Myocardium / cytology
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Myocardium / metabolism*
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Myosin Heavy Chains / biosynthesis*
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Myosin Heavy Chains / genetics
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Phosphorylation / drug effects
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Proto-Oncogene Proteins c-raf / genetics
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Proto-Oncogene Proteins c-raf / metabolism
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Rats
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Reactive Oxygen Species / metabolism*
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Receptor, Angiotensin, Type 1
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Receptor, Angiotensin, Type 2
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Signal Transduction / drug effects
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Transfection
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ras Proteins / genetics
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ras Proteins / metabolism
Substances
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Angiotensin Receptor Antagonists
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Antihypertensive Agents
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Antioxidants
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Fluoresceins
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Fluorescent Dyes
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Reactive Oxygen Species
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Receptor, Angiotensin, Type 1
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Receptor, Angiotensin, Type 2
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Angiotensin II
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diacetyldichlorofluorescein
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Proto-Oncogene Proteins c-raf
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinases
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Myosin Heavy Chains
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ras Proteins